Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

BackgroundSeveral studies indicate that increasing the alimentary limb length in gastric bypass surgery produces only a minor improvement of excess BMI loss. Few studies have addressed the efficacy of increasing the length of the pancreatico-biliary limb.MethodsHere, we present a prospective randomized study of 187 consecutive laparoscopic Roux-Y gastric bypass operations operated over 2 years (2004–2005) in Iceland. The patients were operated with a gastric bypass with either a 2-m biliopancreatic (BP)-limb and a 60-cm alimentary (A)-limb (n = 93) or with a 150-cm A-limb and a 60-cm BP-limb (n = 94).ResultsPreoperative median BMI was 44.1 (38–70), median age 35.5 (17–74) years, and 85 % of the patients were female. Follow-up rate after 5 years was 85 %. Eighteen months following surgery, the weight loss was significantly higher in the BP-limb group (p < 0.001), and this difference remained 7 years after surgery. Weight regain occurred in both groups, and 7 years after surgery, excess BMI loss (EBMIL) was 78.4 % in the BP-limb group compared to 67.1 % in the A-limb group (p < 0.001). Most patients (78 %) needed supplementation adjustment (iron, vitamin D and calcium) during the study period, significantly more often in the BP-limb group compared to the A-limb group (p < 0.001). Patients in the BP-limb group had more frequent stools than patients in the A-limb group; otherwise, gastro-intestinal symptoms rating scoring were comparable. Complication rate was similar.ConclusionsGastric bypass with a 2-m BP-limb gives better weight loss than gastric bypass with a 60-cm BP-limb and a 150-cm A-limb. Metabolic follow-up is of utmost importance, as most patients needed repeated adjustments of their supplementation.

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